JP2736285B2 - 改良したマトリックスメタロプロテアーゼ阻害剤 - Google Patents

改良したマトリックスメタロプロテアーゼ阻害剤

Info

Publication number: JP2736285B2
Authority: JP; Japan
Prior art keywords: alkyl; trp; honhcoch; compound; substituted
Prior art date: 1990-11-21
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

JP4501548A

Other languages

English (en)

Japanese (ja)

Other versions

JPH05508163A (ja

Inventor

イー．ガラーディ，リチャード

グロベルニー，ダミアン

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Individual

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-11-21

Filing date

1991-11-21

Publication date

1998-04-02

1990-11-21 Priority claimed from US07/615,798 external-priority patent/US5183900A/en

1991-11-21 Application filed by Individual filed Critical Individual

1993-11-18 Publication of JPH05508163A publication Critical patent/JPH05508163A/ja

1998-04-02 Application granted granted Critical

1998-04-02 Publication of JP2736285B2 publication Critical patent/JP2736285B2/ja

2013-04-02 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000011159 matrix material Substances 0.000 title claims abstract description 38
239000003475 metalloproteinase inhibitor Substances 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 122
-1 cyclic amine Chemical class 0.000 claims abstract description 58
125000000217 alkyl group Chemical group 0.000 claims abstract description 52
102000005741 Metalloproteases Human genes 0.000 claims abstract description 38
108010006035 Metalloproteases Proteins 0.000 claims abstract description 38
230000000694 effects Effects 0.000 claims abstract description 19
125000003118 aryl group Chemical group 0.000 claims abstract description 14
125000002252 acyl group Chemical group 0.000 claims abstract description 11
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
125000000539 amino acid group Chemical group 0.000 claims abstract description 9
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 3
239000000203 mixture Substances 0.000 claims description 55
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 35
238000002360 preparation method Methods 0.000 claims description 31
238000000034 method Methods 0.000 claims description 28
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
239000003446 ligand Substances 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 10
208000027418 Wounds and injury Diseases 0.000 claims description 9
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 9
239000007787 solid Substances 0.000 claims description 8
230000008685 targeting Effects 0.000 claims description 7
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 6
206010052428 Wound Diseases 0.000 claims description 6
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
206010014989 Epidermolysis bullosa Diseases 0.000 claims description 4
206010040070 Septic Shock Diseases 0.000 claims description 4
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
230000036303 septic shock Effects 0.000 claims description 4
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 3
208000007107 Stomach Ulcer Diseases 0.000 claims description 3
125000004122 cyclic group Chemical group 0.000 claims description 3
150000002443 hydroxylamines Chemical class 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
230000007935 neutral effect Effects 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
241000721454 Pemphigus Species 0.000 claims description 2
208000000453 Skin Neoplasms Diseases 0.000 claims description 2
101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 claims description 2
238000004113 cell culture Methods 0.000 claims description 2
230000001900 immune effect Effects 0.000 claims description 2
238000000338 in vitro Methods 0.000 claims description 2
201000000849 skin cancer Diseases 0.000 claims description 2
125000000547 substituted alkyl group Chemical group 0.000 claims 2
PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical group NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims 1
201000005917 gastric ulcer Diseases 0.000 claims 1
150000001408 amides Chemical group 0.000 abstract description 10
101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
229960004799 tryptophan Drugs 0.000 description 23
210000004087 cornea Anatomy 0.000 description 20
239000003112 inhibitor Substances 0.000 description 20
230000002829 reductive effect Effects 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
230000000875 corresponding effect Effects 0.000 description 18
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 17
102000029816 Collagenase Human genes 0.000 description 16
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238000006243 chemical reaction Methods 0.000 description 13
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KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
229940088598 enzyme Drugs 0.000 description 12
239000002253 acid Substances 0.000 description 11
239000000243 solution Substances 0.000 description 11
239000002904 solvent Substances 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
208000025865 Ulcer Diseases 0.000 description 10
150000001413 amino acids Chemical class 0.000 description 10
BKAJNAXTPSGJCU-UHFFFAOYSA-N 4-methyl-2-oxopentanoic acid Chemical compound CC(C)CC(=O)C(O)=O BKAJNAXTPSGJCU-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
238000011282 treatment Methods 0.000 description 9
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 8
229910052799 carbon Inorganic materials 0.000 description 8
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
241000283973 Oryctolagus cuniculus Species 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
238000003556 assay Methods 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
239000002442 collagenase inhibitor Substances 0.000 description 7
201000010099 disease Diseases 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
238000002347 injection Methods 0.000 description 7
239000007924 injection Substances 0.000 description 7
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
231100000397 ulcer Toxicity 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
210000004969 inflammatory cell Anatomy 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000000047 product Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 5
206010028980 Neoplasm Diseases 0.000 description 5
102000035195 Peptidases Human genes 0.000 description 5
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239000004365 Protease Substances 0.000 description 5
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238000006731 degradation reaction Methods 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
239000006260 foam Substances 0.000 description 5
238000009472 formulation Methods 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
208000024891 symptom Diseases 0.000 description 5
REUDDXCWANRXHG-UHFFFAOYSA-N 2-(2-methoxy-2-oxoethyl)-4-methylpentanoic acid Chemical compound COC(=O)CC(C(O)=O)CC(C)C REUDDXCWANRXHG-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
102000008186 Collagen Human genes 0.000 description 4
108010035532 Collagen Proteins 0.000 description 4
102000013382 Gelatinases Human genes 0.000 description 4
108010026132 Gelatinases Proteins 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
230000001580 bacterial effect Effects 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
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238000002425 crystallisation Methods 0.000 description 4
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230000002500 effect on skin Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000012634 fragment Substances 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
125000001041 indolyl group Chemical group 0.000 description 4
239000010410 layer Substances 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 4
238000000746 purification Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
YCTBLMQFTMPXBD-JTQLQIEISA-N (2s)-2-amino-3-(1h-indol-3-yl)-n-methylpropanamide Chemical compound C1=CC=C2C(C[C@H](N)C(=O)NC)=CNC2=C1 YCTBLMQFTMPXBD-JTQLQIEISA-N 0.000 description 3
AIJWTBCJEORAAK-UHFFFAOYSA-N 1-o-benzyl 4-o-methyl 2-(2-methylpropyl)butanedioate Chemical compound COC(=O)CC(CC(C)C)C(=O)OCC1=CC=CC=C1 AIJWTBCJEORAAK-UHFFFAOYSA-N 0.000 description 3
239000001142 4-methyl-2-oxopentanoic acid Substances 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
230000003313 weakening effect Effects 0.000 description 1
230000029663 wound healing Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Heart & Thoracic Surgery (AREA)
Rheumatology (AREA)
Dermatology (AREA)
Pulmonology (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pain & Pain Management (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Indole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Peptides Or Proteins (AREA)
Quinoline Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Immobilizing And Processing Of Enzymes And Microorganisms (AREA)

JP4501548A 1990-11-21 1991-11-21 改良したマトリックスメタロプロテアーゼ阻害剤 Expired - Lifetime JP2736285B2 (ja)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US07/615,798 US5183900A (en)	1990-11-21	1990-11-21	Matrix metalloprotease inhibitors
US615,798		1990-11-21
US07/747,752 US5189178A (en)	1990-11-21	1991-08-20	Matrix metalloprotease inhibitors
US747,752		1991-08-20

Publications (2)

Publication Number	Publication Date
JPH05508163A JPH05508163A (ja)	1993-11-18
JP2736285B2 true JP2736285B2 (ja)	1998-04-02

Family

ID=27087601

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP4501548A Expired - Lifetime JP2736285B2 (ja)	1990-11-21	1991-11-21	改良したマトリックスメタロプロテアーゼ阻害剤

Country Status (8)

Country	Link
US (1)	US5189178A (de)
EP (1)	EP0558648B1 (de)
JP (1)	JP2736285B2 (de)
AT (1)	ATE265433T1 (de)
AU (1)	AU662504B2 (de)
CA (1)	CA2096221A1 (de)
DE (1)	DE69133385T2 (de)
WO (1)	WO1992009556A1 (de)

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- 1991-08-20 US US07/747,752 patent/US5189178A/en not_active Expired - Lifetime
- 1991-11-21 CA CA002096221A patent/CA2096221A1/en not_active Abandoned
- 1991-11-21 JP JP4501548A patent/JP2736285B2/ja not_active Expired - Lifetime
- 1991-11-21 AU AU90958/91A patent/AU662504B2/en not_active Ceased
- 1991-11-21 DE DE69133385T patent/DE69133385T2/de not_active Expired - Lifetime
- 1991-11-21 EP EP92901322A patent/EP0558648B1/de not_active Expired - Lifetime
- 1991-11-21 WO PCT/US1991/008723 patent/WO1992009556A1/en not_active Ceased
- 1991-11-21 AT AT92901322T patent/ATE265433T1/de not_active IP Right Cessation

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Also Published As

Publication number	Publication date
US5189178A (en)	1993-02-23
EP0558648B1 (de)	2004-04-28
AU662504B2 (en)	1995-09-07
JPH05508163A (ja)	1993-11-18
WO1992009556A1 (en)	1992-06-11
DE69133385D1 (de)	2004-06-03
DE69133385T2 (de)	2005-02-24
AU9095891A (en)	1992-06-25
EP0558648A1 (de)	1993-09-08
EP0558648A4 (en)	1993-11-24
CA2096221A1 (en)	1992-05-22
ATE265433T1 (de)	2004-05-15

Publication	Publication Date	Title
JP2736285B2 (ja)	1998-04-02	改良したマトリックスメタロプロテアーゼ阻害剤
US5239078A (en)	1993-08-24	Matrix metalloprotease inhibitors
US5183900A (en)	1993-02-02	Matrix metalloprotease inhibitors
AU652016B2 (en)	1994-08-11	Treatment for tissue ulceration
US5696147A (en)	1997-12-09	Inhibition of angiogenesis by synthetic matrix metalloprotease inhibitors
US5773438A (en)	1998-06-30	Synthetic matrix metalloprotease inhibitors and use thereof
US5270326A (en)	1993-12-14	Treatment for tissue ulceration
EP0692931A1 (de)	1996-01-24	Synthetische matrix-metalloprotease-inhibitoren und ihre verwendung
AU5778601A (en)	2002-02-07	Synthetic matrix metalloprotease inhibitors and uses thereof
AU8311898A (en)	1999-01-28	Synthetic matrix metalloprotease inhibitors and uses thereof